Role of the active zone protein, ELKS, in insulin secretion from pancreatic β-cells
Role of the active zone protein, ELKS, in insulin secretion from pancreatic β-cells
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活性区蛋白 ELKS 在胰腺 β 细胞分泌胰岛素中的作用
DOI：
10.1016/j.molmet.2019.06.017
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发表时间：
2019
影响因子：
8.1
通讯作者：
Ohtsuka Toshihisa
中科院分区：
文献类型：
--
作者：
Ohara-Imaizumi Mica;Aoyagi Kyota;Ohtsuka Toshihisa
背景胰岛素储存在胰岛β细胞的大颗粒中，随着血糖水平的升高，通过Ca 2+触发的胞吐作用释放。已经提出了胰岛素从胰岛中的β细胞向血管系统的极化和靶向分泌;然而，与细胞和分子定位相关的机制在很大程度上仍然未知。在神经末梢内，极化递质的Ca 2+依赖性释放仅限于活动区，这是突触前膜的高度专门化区域。几种活性区特异性蛋白质已被表征;其中，CAST/ELKS蛋白质家族成员具有与其他活性区蛋白质形成大蛋白质复合物的能力，以控制活性区的结构和功能，从而严格调节神经递质释放。值得注意的是，ELKS而不是CAST也在β细胞中表达，本文综述了ELKS和其他活性区蛋白在胰岛β细胞中的作用，并重点介绍了ELKS调节胰岛极化胰岛素分泌的分子机制。主要结论ELKS定位于血管内皮细胞，其作用机制可能与胰岛β细胞的胰岛素分泌有关。小鼠胰岛β细胞的质膜。ELKS与β细胞面向血管的质膜上的L-型电压依赖性Ca 2+通道形成有效的胰岛素分泌复合物，使极化Ca 2+内流和胰岛的第一时相胰岛素分泌成为可能。该模型提供了对在分子水平上从胰岛内的β细胞分泌胰岛素期间观察到的功能极性的新见解。这种由ELKS在质膜的血管侧形成的活性区样区域对于协调生理胰岛素分泌是必不可少的，并且可能在糖尿病中被破坏。
BackgroundInsulin is stored within large dense-core granules in pancreatic beta (β)-cells and is released by Ca2+-triggered exocytosis with increasing blood glucose levels. Polarized and targeted secretion of insulin from β-cells in pancreatic islets into the vasculature has been proposed; however, the mechanisms related to cellular and molecular localization remain largely unknown. Within nerve terminals, the Ca2+-dependent release of a polarized transmitter is limited to the active zone, a highly specialized area of the presynaptic membrane. Several active zone-specific proteins have been characterized; among them, the CAST/ELKS protein family members have the ability to form large protein complexes with other active zone proteins to control the structure and function of the active zone for tight regulation of neurotransmitter release. Notably, ELKS but not CAST is also expressed in β-cells, implying that ELKS may be involved in polarized insulin secretion from β-cells.Scope of reviewThis review provides an overview of the current findings regarding the role(s) of ELKS and other active zone proteins in β-cells and focuses on the molecular mechanism underlying ELKS regulation within polarized insulin secretion from islets.Major conclusionsELKS localizes at the vascular-facing plasma membrane of β-cells in mouse pancreatic islets. ELKS forms a potent insulin secretion complex with L-type voltage-dependent Ca2+channels on the vascular-facing plasma membrane of β-cells, enabling polarized Ca2+influx and first-phase insulin secretion from islets. This model provides novel insights into the functional polarity observed during insulin secretion from β-cells within islets at the molecular level. This active zone-like region formed by ELKS at the vascular side of the plasma membrane is essential for coordinating physiological insulin secretion and may be disrupted in diabetes.
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影响因子：
4.8
作者：
Fujimoto, K;Shibasaki, T;Seino, S
通讯作者：
Seino, S
健康受试者和糖尿病患者的血浆胰岛素对葡萄糖输注的反应。
DOI：
--
发表时间：
1967
期刊：
Acta Endocrinologica
影响因子：
--
作者：
E. Cerasi;R. Luft
通讯作者：
R. Luft
用生物传感器探测钙离子
影响因子：
--
作者：
J. Nakai;Masamichi Ohkura
通讯作者：
Masamichi Ohkura
影响因子：
7.7
作者：
Barg, S;Eliasson, L;Rorsman, P
通讯作者：
Rorsman, P
影响因子：
4.8
作者：
Ohara-Imaizumi, M;Nakamichi, Y;Nagamatsu, S
通讯作者：
Nagamatsu, S